EP0278174A2 - Use of fluticasone propionate in the preparation of a pharmaceutical composition for the treatment of bowel diseases - Google Patents
Use of fluticasone propionate in the preparation of a pharmaceutical composition for the treatment of bowel diseases Download PDFInfo
- Publication number
- EP0278174A2 EP0278174A2 EP87311250A EP87311250A EP0278174A2 EP 0278174 A2 EP0278174 A2 EP 0278174A2 EP 87311250 A EP87311250 A EP 87311250A EP 87311250 A EP87311250 A EP 87311250A EP 0278174 A2 EP0278174 A2 EP 0278174A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- treatment
- fluticasone propionate
- disease
- pharmaceutical composition
- bowel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- This invention relates to pharmaceutical compositions for use in the treatment of inflammatory bowel diseases and other bowel diseases which respond to treatment with glucocorticoid steroids, for example celiac disease.
- Inflammatory bowel disease is the term generally applied to two diseases, namely ulcerative colitis and Crohn's disease.
- Ulcerative colitis is a chronic inflammatory disease of unknown aetiology afflicting only the large bowel and, except when very severe, limited to the bowel mucosa.
- the course of the disease may be continuous or relapsing, mild or severe. It is curable by total colectomy which may be needed for acute severe disease or chronic unremitting disease.
- Most patients with ulcerative colitis are managed medically rather than surgically.
- Crohn's disease is also a chronic inflammatory disease of unknown aetiology but, unlike ulcerative colitis, it can affect any part of the bowel. Although lesions may start superficially, the inflammatory process extends through the bowel wall to the draining lymph nodes. As with ulcerative colitis, the course of the disease may be continuous or relapsing, mild or severe but, unlike ulcerative colitis it is not curable by resection of the involved segment of bowel. Most patients with Crohn's disease come to surgery at some time, but subsequent relapse is common and continuous medical treatment is usual.
- glucocorticoid steroids such as prednisone or prednisolone acetate are almost invariably used and given by mouth for the average acute attack or relapse, or locally, by enema.
- sulphasalazine is the maintenance treatment of choice in treating ulcerative colitis.
- This drug has a significant number of side effects chiefly due to absorption of the sulphapyridine moiety from the colon.
- Recently compounds which contain only 5-amino-salicylic acid have been developed; these are as effective as sulphasalazine and do not have the sulphapyridine side effects but do have side effects of their own, notably diarrhoea.
- Glucocorticoid steriods are, however, not used for maintenance of remission in ulcerative colitis; doses that do not produce unacceptable side effects are ineffective, and patients who need chronic high dose glucocorticoid steroids for control of their disease almost invariably are treated by colectomy.
- glucocorticoid steroids are the treatment of choice for severe active Crohn's disease, but ideally only to achieve remission, after which they should be stopped. However, all too frequently the disease does not satisfactorily remit, and glucocorticoid steroids may be necessary to maintain control of symptoms. Sulphasalazine is also useful in less severe cases, particularly for disease involving the colon.
- Celiac disease is a chronic intestinal disorder caused by a specific intolerance to gluten present in wheat and rye proteins leading to changes in the small intestinal mucosa and impaired absorption.
- Current treatment is effected by a well balanced gluten-gliadin free diet high in calories and proteins and normal in fat. This excludes cereal grains with the exception of rice and corn.
- glucocorticoid steroids such as hydrocortisone, prednisone or prednisolone.
- Fluticasone propionate is described and claimed in United Kingdom Patent Specification 2088877B and shows good anti-inflammatory activity on topical application and may be used in anti-inflammatory therapy, for example, by topical application to the skin, for the treatment of inflammatory dermatoses of humans and animals, for example eczema, which are normally responsive to glucocorticoid steroid therapy, and also of less responsive conditions such as psoriasis in humans.
- the active glucocorticoid steroids which include fluticasone propionate, may in general be given by internal administration, including oral or rectal administration; however this is only in the context of cases where systemic adrenocortical therapy is indicated. There is no suggestion that the active glucocorticoid steroids would be of use in treating inflammatory diseases of the bowel or other bowel diseases such as celiac disease.
- fluticasone propionate unlike other glucocorticoid steroids used in the treatment of inflammatory bowel disease and contrary to the teaching of the above United Kingdom patent specification, is poorly absorbed from the gastrointestinal tract; furthermore it appears to be rapidly metabolised even when absorbed and its systemic effects from the oral route are negligible.
- Fluticasone propionate thus potentially represents a very significant advance over other glucocorticoid steroids which exert their effects systemically and other drugs previously used for the management of Crohn's disease and celiac disease, particularly in avoiding the systemic side effects normally associated with glucocorticoid steroid therapy.
- the virtual non-absorption of the drug renders possible its safe use in the maintenance therapy of the disease as well as achieving remission in the acute phase.
- Crohn's disease is not a very common condition, it is a chronic and often debilitating disorder that can benefit from a safer and more effective treatment.
- fluticasone propionate may help to reduce the number of patients having to undergo surgery and in addition, its lack of systemic effects makes it possible to use the drug for maintenance therapy once remission has been achieved.
- the invention therefore provides pharmaceutical compositions comprising fluticasone propionate for use in the treatment by the oral, stomal or rectal route of bowel diseases which respond to treatment with glucocorticoid steroids.
- the invention also provides the use of fluticasone propionate in the preparation of pharmaceutical compositions for the treatment by the oral, stomal or rectal route of bowel diseases which respond to treatment with glucocorticoid steroids.
- the invention further provides a method of treatment of bowel diseases which respond to treatment with glucocorticoid steroids wherein an effective dose of fluticasone propionate is administered by the oral, stomal or rectal route to a human or animal subject suffering from said bowel disease responsive to glucocorticoid steroids.
- the invention is particularly applicable to inflammatory bowel disease as hereinbefore defined, and celiac disease.
- the pharmaceutical composition can be in the form of suspensions, capsules or tablets, and can be formulated by conventional methods.
- fluticasone propionate should be formulated so that it is released preferentially in the colon.
- fluticasone propionate may also be formulated so that it is released preferentially in the upper small bowel or stomach.
- compositions are slow, delayed or positioned release tablets or capsules, in particular tablets or capsules having an enteric coating, that is a coating resistant to conditions within the stomach but releasing the contents in the colon.
- enteric coating that is a coating resistant to conditions within the stomach but releasing the contents in the colon.
- Such formulations are novel, and constitute a further feature of the invention; any previous disclosure of oral formulations of fluticasone propionate, for example in our above United Kingdom Patent Specification, have been in the context of systemic anti-inflammatory activity and there has been no previous proposal to formulate fluticasone propionate in delayed release, positioned release or enteric coated tablets. These would not, of course, have been thought necessary or desirable merely for systemic absorption.
- Suitable compositions for delayed release or enteric coated oral formulations include tablet formulations film coated with materials that are water resistant, pH sensitive, digested or emulsified by intestinal juices or sloughed off at a slow but regular rate when moistened.
- suitable coating materials are combinations of hydroxypropyl methylcellulose and ethyl cellulose, cellulose acetate phthalate; polyvinyl acetate phthalate; hydroxypropyl methylcellulose phthalate; polymers of methacrylic acid and its esters. These coating materials may be used alone or in combination to achieve the required release characteristics.
- Plasticisers such as polyethylene glycol, dibutylphthalate, triacetin and castor oil may be used.
- a pigment may also be used to colour the film.
- materials may be incorporated into the matrix of the tablet e.g. hydroxypropyl methylcellulose; ethyl cellulose or polymers of acrylic and methacrylic acid esters. These latter materials may also be applied to tablets by compression coating.
- the dosage range for treatment of inflammatory bowel disease and celiac disease is suitably 2-40 mg per day, preferably 10-30 mg per day for adults and 2-15 mg per day for children.
- a convenient daily dose by the oral route would be of the order of 2mg to 20mg per day, depending on the condition of the patient, advantageously in the form of dosage units containing from 1mg to 10mg per dosage unit, preferably 1mg to 5mg per dosage unit.
- a convenient regimen in the case of a slow release, delayed release or positioned release tablet would be 1,2,3 or 4 times a day depending on the condition of the patient.
- the daily dosage may preferably be in the range 10mg to 20mg per day, while for maintenance therapy, the daily dose may preferably be in the range 2mg to 10mg per day.
- the pharmaceutical composition could also be in a form suitable for stomal or rectal administration for example as an enema in a suitable buffered aqueous vehicle, or as suppositories prepared for example with commercial suppository bases.
- the daily dose would be of the order of 2mg to 15mg per day, preferably 10mg to 15mg per day for the acute phase and 2mg to 10mg per day for maintenance therapy.
- compositions comprising fluticasone propionate can be used in the treatment of bowel diseases according to the invention.
- Tablets may be prepared by the normal methods such as direct compression or wet granulation.
- the active ingredient is blended with the lactose, croscarmellose sodium and magnesium stearate.
- the resultant mix is compressed into tablets using 5.5mm diameter punches.
- Tablets of other strengths may be prepared by altering the ratio of active ingredient to lactose or the compression weight and using punches to suit.
- the tablets are film coated with the following film coating suspension using suitable film coating equipment to give a weight of film coat of approximatly 5mg.
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Abstract
Description
- This invention relates to pharmaceutical compositions for use in the treatment of inflammatory bowel diseases and other bowel diseases which respond to treatment with glucocorticoid steroids, for example celiac disease.
- Inflammatory bowel disease is the term generally applied to two diseases, namely ulcerative colitis and Crohn's disease.
- Ulcerative colitis is a chronic inflammatory disease of unknown aetiology afflicting only the large bowel and, except when very severe, limited to the bowel mucosa. The course of the disease may be continuous or relapsing, mild or severe. It is curable by total colectomy which may be needed for acute severe disease or chronic unremitting disease. Most patients with ulcerative colitis are managed medically rather than surgically.
- Crohn's disease is also a chronic inflammatory disease of unknown aetiology but, unlike ulcerative colitis, it can affect any part of the bowel. Although lesions may start superficially, the inflammatory process extends through the bowel wall to the draining lymph nodes. As with ulcerative colitis, the course of the disease may be continuous or relapsing, mild or severe but, unlike ulcerative colitis it is not curable by resection of the involved segment of bowel. Most patients with Crohn's disease come to surgery at some time, but subsequent relapse is common and continuous medical treatment is usual.
- For treatment of acute attacks of ulcerative colitis, glucocorticoid steroids such as prednisone or prednisolone acetate are almost invariably used and given by mouth for the average acute attack or relapse, or locally, by enema.
- After remission has been achieved, sulphasalazine is the maintenance treatment of choice in treating ulcerative colitis. This drug, however, has a significant number of side effects chiefly due to absorption of the sulphapyridine moiety from the colon. Recently compounds which contain only 5-amino-salicylic acid have been developed; these are as effective as sulphasalazine and do not have the sulphapyridine side effects but do have side effects of their own, notably diarrhoea.
- Glucocorticoid steriods are, however, not used for maintenance of remission in ulcerative colitis; doses that do not produce unacceptable side effects are ineffective, and patients who need chronic high dose glucocorticoid steroids for control of their disease almost invariably are treated by colectomy.
- As with ulcerative colitis, glucocorticoid steroids are the treatment of choice for severe active Crohn's disease, but ideally only to achieve remission, after which they should be stopped. However, all too frequently the disease does not satisfactorily remit, and glucocorticoid steroids may be necessary to maintain control of symptoms. Sulphasalazine is also useful in less severe cases, particularly for disease involving the colon.
- Very often in Crohn's disease, however, primary medical treatment of the disease process is ineffective, and only symptomatic treatment is of value i.e. analgesics for pain and opiates for diarrhoea. Most patients eventually require surgery.
- Celiac disease is a chronic intestinal disorder caused by a specific intolerance to gluten present in wheat and rye proteins leading to changes in the small intestinal mucosa and impaired absorption. Current treatment is effected by a well balanced gluten-gliadin free diet high in calories and proteins and normal in fat. This excludes cereal grains with the exception of rice and corn. Those patients with celiac disease who do not respond to the gluten- gliadin free diet are given glucocorticoid steroids such as hydrocortisone, prednisone or prednisolone.
- Our studies indicate that these diseases may advantageously be treated using the anti-inflammatory steroid S-fluoromethyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxoandrosta-1,4-diene-17β-carbothioate, which has the approved name "fluticasone propionate".
- Fluticasone propionate is described and claimed in United Kingdom Patent Specification 2088877B and shows good anti-inflammatory activity on topical application and may be used in anti-inflammatory therapy, for example, by topical application to the skin, for the treatment of inflammatory dermatoses of humans and animals, for example eczema, which are normally responsive to glucocorticoid steroid therapy, and also of less responsive conditions such as psoriasis in humans.
- The above United Kingdom Patent Specification also indicates that the active glucocorticoid steroids, which include fluticasone propionate, may in general be given by internal administration, including oral or rectal administration; however this is only in the context of cases where systemic adrenocortical therapy is indicated. There is no suggestion that the active glucocorticoid steroids would be of use in treating inflammatory diseases of the bowel or other bowel diseases such as celiac disease.
- We have surprisingly found that fluticasone propionate, unlike other glucocorticoid steroids used in the treatment of inflammatory bowel disease and contrary to the teaching of the above United Kingdom patent specification, is poorly absorbed from the gastrointestinal tract; furthermore it appears to be rapidly metabolised even when absorbed and its systemic effects from the oral route are negligible.
- These advantageous properties are of great potential benefit in the treatment of inflammatory bowel disease. Thus, it is possible for the drug to reach the inflamed site in the bowel in sufficient concentration to exert direct anti-inflammatory therapeutic action for a relatively long time with the possibility of systemic side effects being greatly reduced or even eliminated.
- Fluticasone propionate thus potentially represents a very significant advance over other glucocorticoid steroids which exert their effects systemically and other drugs previously used for the management of Crohn's disease and celiac disease, particularly in avoiding the systemic side effects normally associated with glucocorticoid steroid therapy. The virtual non-absorption of the drug renders possible its safe use in the maintenance therapy of the disease as well as achieving remission in the acute phase. Although Crohn's disease is not a very common condition, it is a chronic and often debilitating disorder that can benefit from a safer and more effective treatment.
- In ulcerative colitis, fluticasone propionate may help to reduce the number of patients having to undergo surgery and in addition, its lack of systemic effects makes it possible to use the drug for maintenance therapy once remission has been achieved.
- The invention therefore provides pharmaceutical compositions comprising fluticasone propionate for use in the treatment by the oral, stomal or rectal route of bowel diseases which respond to treatment with glucocorticoid steroids.
- The invention also provides the use of fluticasone propionate in the preparation of pharmaceutical compositions for the treatment by the oral, stomal or rectal route of bowel diseases which respond to treatment with glucocorticoid steroids.
- The invention further provides a method of treatment of bowel diseases which respond to treatment with glucocorticoid steroids wherein an effective dose of fluticasone propionate is administered by the oral, stomal or rectal route to a human or animal subject suffering from said bowel disease responsive to glucocorticoid steroids.
- The invention is particularly applicable to inflammatory bowel disease as hereinbefore defined, and celiac disease.
- For oral administration, the pharmaceutical composition can be in the form of suspensions, capsules or tablets, and can be formulated by conventional methods. Ideally, in ulcerative colitis, fluticasone propionate should be formulated so that it is released preferentially in the colon. Alternatively, in Crohn's disease fluticasone propionate may also be formulated so that it is released preferentially in the upper small bowel or stomach.
- The most preferred compositions are slow, delayed or positioned release tablets or capsules, in particular tablets or capsules having an enteric coating, that is a coating resistant to conditions within the stomach but releasing the contents in the colon. Such formulations are novel, and constitute a further feature of the invention; any previous disclosure of oral formulations of fluticasone propionate, for example in our above United Kingdom Patent Specification, have been in the context of systemic anti-inflammatory activity and there has been no previous proposal to formulate fluticasone propionate in delayed release, positioned release or enteric coated tablets. These would not, of course, have been thought necessary or desirable merely for systemic absorption.
- Suitable compositions for delayed release or enteric coated oral formulations include tablet formulations film coated with materials that are water resistant, pH sensitive, digested or emulsified by intestinal juices or sloughed off at a slow but regular rate when moistened. Examples of suitable coating materials are combinations of hydroxypropyl methylcellulose and ethyl cellulose, cellulose acetate phthalate; polyvinyl acetate phthalate; hydroxypropyl methylcellulose phthalate; polymers of methacrylic acid and its esters. These coating materials may be used alone or in combination to achieve the required release characteristics. Plasticisers such as polyethylene glycol, dibutylphthalate, triacetin and castor oil may be used. A pigment may also be used to colour the film.
- Alternatively, materials may be incorporated into the matrix of the tablet e.g. hydroxypropyl methylcellulose; ethyl cellulose or polymers of acrylic and methacrylic acid esters. These latter materials may also be applied to tablets by compression coating.
- The dosage range for treatment of inflammatory bowel disease and celiac disease is suitably 2-40 mg per day, preferably 10-30 mg per day for adults and 2-15 mg per day for children.
- A convenient daily dose by the oral route would be of the order of 2mg to 20mg per day, depending on the condition of the patient, advantageously in the form of dosage units containing from 1mg to 10mg per dosage unit, preferably 1mg to 5mg per dosage unit. A convenient regimen in the case of a slow release, delayed release or positioned release tablet would be 1,2,3 or 4 times a day depending on the condition of the patient. In the acute phase, the daily dosage may preferably be in the range 10mg to 20mg per day, while for maintenance therapy, the daily dose may preferably be in the range 2mg to 10mg per day.
- The pharmaceutical composition could also be in a form suitable for stomal or rectal administration for example as an enema in a suitable buffered aqueous vehicle, or as suppositories prepared for example with commercial suppository bases. In the case of stomal or rectal administration the daily dose would be of the order of 2mg to 15mg per day, preferably 10mg to 15mg per day for the acute phase and 2mg to 10mg per day for maintenance therapy.
- The following pharmaceutical compositions comprising fluticasone propionate can be used in the treatment of bowel diseases according to the invention.
-
- The active ingredient is blended with the lactose, croscarmellose sodium and magnesium stearate. The resultant mix is compressed into tablets using 5.5mm diameter punches.
- Tablets of other strengths may be prepared by altering the ratio of active ingredient to lactose or the compression weight and using punches to suit.
-
- ** A proprietary aqueous film coating material consisting of a 30% w/w dispersion of a copolymer of polymethacrylic acid and acrylic acid esters obtained from Röhm Pharma.
-
- Slurry the fluticasone propionate in a solution of polysorbate 80 in a small proportion of the water. Dissolve the sodium saccharin and sodium chloride in the bulk of the water. Add the fluticasone propionate slurry to the bulk solution and mix. Make up to volume with water and mix.
- 5mls or multiples thereof.
-
- Slurry the fluticasone propionate in a solution of the polysorbate 80 in a small proportion of the water. Disperse the Avicel in about 20% of the water. Heat the bulk of the water to 70°C, add and dissolve the p-hydroxy benzoates. Add and dissolve the disodium hydrogen phosphate, citric acid, sodium saccharin and sodium chloride, cool, add the Avicel dispersion followed by the fluticasone propionate slurry. Mix and make up to volume with water.
- (ii) As, (i) substituting benzoic acid 0.1% for the p-hydroxybenzoates.
-
- Heat most of the water to 75°C, dissolve the p-hydroxybenzoates followed by the disodium hydrogen phosphate and citric acid. Melt together the cetostearyl alcohol, most of the cetomacrogol and the liquid paraffin, heating the mixture to 70°C. Add this mixture to the hot aqueous phase (70 to 75°C), stir and cool to 50°C.
- Slurry the fluticasone propionate in a small proportion of the water containing a small portion of the cetomacrogol. Add the slurry to the bulk with stirring while the latter is at 50°C. Continue stirring while cooling until a temperature of 35°C is reached.
- Fill 100ml aliquots into bottles or enema bags.
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT87311250T ATE86491T1 (en) | 1986-12-24 | 1987-12-21 | USE OF FLUTICASONE PROPIONATE IN THE MANUFACTURE OF A MEDICATION FOR THE TREATMENT OF ENTERTAIN DISEASES. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8630913 | 1986-12-24 | ||
GB868630913A GB8630913D0 (en) | 1986-12-24 | 1986-12-24 | Pharmaceutical compositions |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0278174A2 true EP0278174A2 (en) | 1988-08-17 |
EP0278174A3 EP0278174A3 (en) | 1990-06-27 |
EP0278174B1 EP0278174B1 (en) | 1993-03-10 |
Family
ID=10609600
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP87311250A Expired - Lifetime EP0278174B1 (en) | 1986-12-24 | 1987-12-21 | Use of fluticasone propionate in the preparation of a pharmaceutical composition for the treatment of bowel diseases |
Country Status (13)
Country | Link |
---|---|
US (1) | US4985418A (en) |
EP (1) | EP0278174B1 (en) |
JP (1) | JPS63233998A (en) |
KR (1) | KR880007084A (en) |
AT (1) | ATE86491T1 (en) |
AU (1) | AU8296987A (en) |
CA (1) | CA1302262C (en) |
DE (1) | DE3784693T2 (en) |
DK (1) | DK678887A (en) |
ES (1) | ES2053571T3 (en) |
GB (2) | GB8630913D0 (en) |
NZ (1) | NZ223045A (en) |
ZA (1) | ZA879464B (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991007172A1 (en) * | 1989-11-22 | 1991-05-30 | Aktiebolaget Draco | Oral composition for the treatment of inflammatory bowel diseases |
WO1994012187A1 (en) * | 1992-11-20 | 1994-06-09 | Valeas S.P.A. Industria Chimica E Farmaceutica | Rectal flunisolide compositions for treating inflammatory intestinal disorders |
US5643602A (en) * | 1989-11-22 | 1997-07-01 | Astra Aktiebolag | Oral composition for the treatment of inflammatory bowel disease |
WO1999056698A2 (en) * | 1998-05-06 | 1999-11-11 | Københavns Universitet | Treatment of celiac disease |
US6432967B1 (en) | 1995-03-30 | 2002-08-13 | Mayo Foundation For Medical Education & Research | Enema and enterically-coated oral dosage forms of azathioprine |
WO2005004873A1 (en) * | 2003-07-10 | 2005-01-20 | Icn Pharmaceuticals Switzerland Ltd. | Use of antivirals against inflammatory bowel diseases |
US8865688B2 (en) | 2008-10-03 | 2014-10-21 | Dr. Falk Pharma Gmbh | Compositions and methods for treatment of bowel diseases with granulated mesalamine |
US8911778B2 (en) | 1997-07-30 | 2014-12-16 | Dr. Falk Pharma Gmbh | Pellet formulation for the treatment of the intestinal tract |
US9974752B2 (en) | 2014-10-31 | 2018-05-22 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
US10722473B2 (en) | 2018-11-19 | 2020-07-28 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5208226A (en) * | 1989-09-08 | 1993-05-04 | Glaxo Group Limited | Medicaments |
US5270305A (en) * | 1989-09-08 | 1993-12-14 | Glaxo Group Limited | Medicaments |
NL1006774C2 (en) * | 1996-08-14 | 1998-09-28 | Univ Potchefstroom | Anti-atherosclerosis and anti-thrombotic agent and its uses. |
US5993782A (en) * | 1998-04-28 | 1999-11-30 | Gardner; Conrad O. | Therapeutic method for reversing hyposmia in a human patient |
GB9823036D0 (en) * | 1998-10-22 | 1998-12-16 | Glaxo Group Ltd | Fluticasone lotion having improved vasoconstrictor activity |
US6667344B2 (en) | 2001-04-17 | 2003-12-23 | Dey, L.P. | Bronchodilating compositions and methods |
US20040023935A1 (en) * | 2002-08-02 | 2004-02-05 | Dey, L.P. | Inhalation compositions, methods of use thereof, and process for preparation of same |
US20040109826A1 (en) * | 2002-12-06 | 2004-06-10 | Dey, L.P. | Stabilized albuterol compositions and method of preparation thereof |
TWI359675B (en) * | 2003-07-10 | 2012-03-11 | Dey L P | Bronchodilating β-agonist compositions |
US8679545B2 (en) | 2005-11-12 | 2014-03-25 | The Regents Of The University Of California | Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract |
US8324192B2 (en) | 2005-11-12 | 2012-12-04 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US8497258B2 (en) * | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US9050368B2 (en) * | 2007-11-13 | 2015-06-09 | Meritage Pharma, Inc. | Corticosteroid compositions |
GB2458403B (en) | 2007-11-13 | 2010-01-13 | Meritage Pharma Inc | Stabilised corticosteroid compositions |
US20100216754A1 (en) * | 2007-11-13 | 2010-08-26 | Meritage Pharma, Inc. | Compositions for the treatment of inflammation of the gastrointestinal tract |
EP2440210A4 (en) * | 2009-06-12 | 2014-01-29 | Meritage Pharma Inc | Methods for treating gastrointestinal disorders |
CN106421797A (en) * | 2009-10-01 | 2017-02-22 | 艾戴尔医药公司 | Orally administered corticosteroid compositions |
WO2015034678A2 (en) | 2013-09-06 | 2015-03-12 | Aptalis Pharmatech, Inc. | Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis |
TWI728172B (en) | 2016-08-18 | 2021-05-21 | 美商愛戴爾製藥股份有限公司 | Methods of treating eosinophilic esophagitis |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2088877A (en) * | 1980-02-15 | 1982-06-16 | Glaxo Group Ltd | Androstane 17 beta carbothioates |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE887518A (en) * | 1980-02-15 | 1981-08-13 | Glaxo Group Ltd | ANDROSTAN CARTOTHIOATES |
US4578221A (en) * | 1980-04-23 | 1986-03-25 | Glaxo Group Limited | Androstane carbothioic acids |
US4710495A (en) * | 1980-07-10 | 1987-12-01 | Otsuka Pharmaceutical Co., Ltd. | Soft steroids having anti-inflammatory activity |
-
1986
- 1986-12-24 GB GB868630913A patent/GB8630913D0/en active Pending
-
1987
- 1987-12-17 ZA ZA879464A patent/ZA879464B/en unknown
- 1987-12-21 GB GB8729756A patent/GB2199747B/en not_active Expired - Fee Related
- 1987-12-21 EP EP87311250A patent/EP0278174B1/en not_active Expired - Lifetime
- 1987-12-21 ES ES87311250T patent/ES2053571T3/en not_active Expired - Lifetime
- 1987-12-21 AT AT87311250T patent/ATE86491T1/en not_active IP Right Cessation
- 1987-12-21 DE DE8787311250T patent/DE3784693T2/en not_active Expired - Fee Related
- 1987-12-22 NZ NZ223045A patent/NZ223045A/en unknown
- 1987-12-22 DK DK678887A patent/DK678887A/en not_active Application Discontinuation
- 1987-12-23 JP JP62324203A patent/JPS63233998A/en active Pending
- 1987-12-23 AU AU82969/87A patent/AU8296987A/en not_active Abandoned
- 1987-12-23 US US07/137,169 patent/US4985418A/en not_active Expired - Lifetime
- 1987-12-23 CA CA000555200A patent/CA1302262C/en not_active Expired - Lifetime
- 1987-12-24 KR KR870014856A patent/KR880007084A/en not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2088877A (en) * | 1980-02-15 | 1982-06-16 | Glaxo Group Ltd | Androstane 17 beta carbothioates |
Non-Patent Citations (2)
Title |
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THE MERCK MANNUAL, 14th edition, 1982, pages 775-777, edited by R. Berkow, Merck & Co., Rahway, US; "Celiac disease" * |
THE MERCK MANNUAL, 14th edition, 1982, pages 780-788, edited by R. Berkow, Merck & Co., Rahway, US; "Chronic inflammatory diseases of the bowel" * |
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US6423340B1 (en) | 1989-11-22 | 2002-07-23 | Aktiebolaget Draco | Method for the treatment of inflammatory bowel diseases |
US5643602A (en) * | 1989-11-22 | 1997-07-01 | Astra Aktiebolag | Oral composition for the treatment of inflammatory bowel disease |
WO1991007172A1 (en) * | 1989-11-22 | 1991-05-30 | Aktiebolaget Draco | Oral composition for the treatment of inflammatory bowel diseases |
WO1994012187A1 (en) * | 1992-11-20 | 1994-06-09 | Valeas S.P.A. Industria Chimica E Farmaceutica | Rectal flunisolide compositions for treating inflammatory intestinal disorders |
US5721228A (en) * | 1992-11-20 | 1998-02-24 | Valeas S.P.A. Industria Chimica E Farmaceutica | Rectal flunisolide compositions for treating inflammatory intestinal disorders |
US6432967B1 (en) | 1995-03-30 | 2002-08-13 | Mayo Foundation For Medical Education & Research | Enema and enterically-coated oral dosage forms of azathioprine |
US8956647B2 (en) | 1997-07-30 | 2015-02-17 | Dr. Falk Pharma Gmbh | Pellet formulation for the treatment of the intestinal tract |
US8911778B2 (en) | 1997-07-30 | 2014-12-16 | Dr. Falk Pharma Gmbh | Pellet formulation for the treatment of the intestinal tract |
US8940328B2 (en) | 1997-07-30 | 2015-01-27 | Dr. Falk Pharma Gmbh | Pellet formulation for the treatment of the intestinal tract |
WO1999056698A3 (en) * | 1998-05-06 | 1999-12-29 | Univ Koebenhavn | Treatment of celiac disease |
WO1999056698A2 (en) * | 1998-05-06 | 1999-11-11 | Københavns Universitet | Treatment of celiac disease |
WO2005004873A1 (en) * | 2003-07-10 | 2005-01-20 | Icn Pharmaceuticals Switzerland Ltd. | Use of antivirals against inflammatory bowel diseases |
US8865688B2 (en) | 2008-10-03 | 2014-10-21 | Dr. Falk Pharma Gmbh | Compositions and methods for treatment of bowel diseases with granulated mesalamine |
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Also Published As
Publication number | Publication date |
---|---|
GB2199747A (en) | 1988-07-20 |
US4985418A (en) | 1991-01-15 |
GB2199747B (en) | 1990-10-24 |
DK678887D0 (en) | 1987-12-22 |
EP0278174A3 (en) | 1990-06-27 |
ZA879464B (en) | 1988-12-28 |
NZ223045A (en) | 1989-11-28 |
DE3784693T2 (en) | 1993-06-17 |
KR880007084A (en) | 1988-08-26 |
GB8630913D0 (en) | 1987-02-04 |
CA1302262C (en) | 1992-06-02 |
ES2053571T3 (en) | 1994-08-01 |
GB8729756D0 (en) | 1988-02-03 |
EP0278174B1 (en) | 1993-03-10 |
ATE86491T1 (en) | 1993-03-15 |
AU8296987A (en) | 1988-06-30 |
JPS63233998A (en) | 1988-09-29 |
DE3784693D1 (en) | 1993-04-15 |
DK678887A (en) | 1988-06-25 |
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